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 Practitioners

should not focus only on the specific clinical findings associated

with a toxidrome. Rather, they should consider all subjective

and objective data gathered from the history of exposure, the

patient’s medical history, physical examination, and laboratory

findings.30

INTERPRETATION OF LABORATORY DATA

DRUG SCREENS

A urine drug screen can be useful in identifying the presence

of drugs and their metabolites in selected patients but is not

indicated in all cases of drug overdose. Urine drug screens can

be useful in a patient with coma of unknown etiology, when the

presented history is inconsistent with clinical findings, or when

more than one drug might have been ingested.35,36

PHARMACOKINETIC CONSIDERATIONS

The absorption, distribution, metabolism, and elimination of

drugs in the overdosed patient can be quite different than

when the drug is taken in usual therapeutic doses.32–34 The

expected pharmacodynamic and pharmacokinetic features of

drugs can be substantially altered by large drug overdoses, especially with drugs that exhibit dose-dependent pharmacokinetics.

The rate of drug absorption is generally slowed by large overdoses, and the time to reach peak serum drug concentrations

can be delayed.35,37 For example, peak serum concentrations of

phenytoin can be delayed for 2 to 7 days after an orally ingested

overdose.38,39 The volume of distribution of an overdosed drug

can be increased, and when usual metabolic pathways become

saturated, secondary clearance pathways can be important. For

example, large overdoses of acetaminophen saturate glutathione

mechanisms of metabolism, resulting in hepatotoxicity.40

When the pharmacokinetic parameters of an overdosed drug

are altered, serial plasma concentration measurements can better define the absorption, distribution, and clearance phases of

the ingested substance. Pharmacokinetic parameters that have

been derived from therapeutic doses should not be used to predict whether absorption is complete or to predict the expected

duration of intoxication caused by large overdoses.34,41,42

DECONTAMINATION

After the airway and the cardiopulmonary system are supported,

efforts should be directed toward removing the toxic substance

from the patient (i.e., decontamination).25,43 Decontamination

presumes that both the dose and the duration of toxin exposure are important in determining the extent of toxicity and that

prevention of continued exposure will decrease toxicity.32–34,43

This intuitive concept is clearly relevant to ocular, dermal, and

respiratory exposures, when local tissue damage is the primary

problem. Respiratory decontamination involves removing the

patient from the toxic environment and providing fresh air or

oxygen to the patient. Decontamination of skin and eyes involves

flushing the affected area with large volumes of water or saline

to physically remove the toxic substance from the surface.25,26

GASTROINTESTINAL DECONTAMINATION

Because most poisonings and overdoses result from oral ingestions, measures to decrease or prevent continued GI absorption

have commonly been used to limit the extent of exposure.25,26,40

GI decontamination should be considered if the ingestion is large

enough to produce potentially significant toxicity, or if the potential severity of the ingestion is unknown and the time since ingestion is less than1 hour. The following methods have historically

been used: (a) evacuation of gastric contents by emesis or gastric

lavage, (b) administration of activated charcoal as an adsorbent

to bind the toxic substance remaining in the GI tract, (c) use of

cathartics or whole bowel irrigation (WBI) to increase the rectal

elimination of unabsorbed drug, or (d) a combination of any of

these methods.44–49

For a PowerPoint presentation about GI

decontamination, go to http://thepoint.

lww.com/AT10e.

The efficacy of GI decontamination varies, depending on

when the process is initiated relative to the time of ingestion,

dose ingested, and other factors. Furthermore, ipecac-induced

emesis, gastric lavage, cathartics, and activated charcoal are not

directly associated with improved patient outcomes.44–49

The most appropriate method for GI tract decontamination remains unclear because sound comparative data for different methods of GI decontamination are not available. Clinical research in healthy subjects, by necessity, must use nontoxic

doses of drugs. Studies using nontoxic doses are not applicable to

the overdose situation because alterations in GI absorption can

occur with large doses. In addition, low-dose studies generally

rely on pharmacokinetic end points such as peak plasma concentrations, area under the plasma concentration–time curve, or

quantity of drug recovered from the urine.44,45,47–49 In contrast,

clinical studies of GI decontamination methods in patients who

have ingested toxic doses of a substance use clinical outcomes

or a directional change in serum drug concentrations.44,45,48,49

These latter trials are not standardized with respect to the dose

ingested or to the time interval between drug ingestion and

GI decontamination.44–49

Ipecac-Induced Emesis and Gastric Lavage

Ipecac-induced emesis and gastric lavage primarily remove substances from the stomach. Their efficacy is affected significantly

by the time the ingested substance remains in the stomach. Gastric lavage and ipecac-induced emesis are most effective when

implemented before the substance moves past the stomach into

the intestine (usually within 1 hour).44,45

The commonly used adult gastric lavage tube (36F) has an

internal diameter too small to allow recovery of large tablet or

capsule fragments. An even smaller diameter lavage tube is used

for children.45 Gastric lavage may be useful only if large amounts

of a liquid substance were ingested and the patient arrived within

1 hour of the ingestion.45 However, patients usually arrive in

the ED more than an hour after ingestion, when absorption

of the toxin has most likely already occurred. As a result, the

efficacy of these procedures in overdose situations is minimal,

and no studies have confirmed that use of gastric lavage or ipecacinduced emesis improves the outcome of the patient.44,45,50 For

these reasons, ipecac is no longer used, and gastric lavage is used

only in rare, specific situations.

Activated Charcoal

In 1963, a review article concluded that activated charcoal was the

most valuable agent available for the treatment of poisoning.51

70 Section 1 General Care

This conclusion was based only on studies in fasting patients who

had nontoxic exposures. Nevertheless, data from those studies

were extrapolated to poisoned patients. Since then, activated

charcoal has become the preferred method of GI decontamination for the treatment of toxic ingestions.25,43,51–53

The goal of therapy is to decrease the absorption of the substance and reduce or prevent systemic toxicity.46 Unfortunately,

there are no satisfactorily designed clinical studies assessing benefit from the use of activated charcoal to guide the use of this

therapy. There is also no evidence that the administration of

activated charcoal improves clinical outcomes.46

The use of activated charcoal at a dose of 1 g/kg should be

considered when the patient has ingested a toxic substance that is

known to be absorbed by activated charcoal within 1 hour of the

ingestion. The potential for benefit is unknown if the activated

charcoal is given more than 1 hour after ingestion.46 It should

be noted that iron and lithium are not absorbed by activated

charcoal. Other forms of GI decontamination must be used to

remove those substances from the GI tract.46

Generally the use of activated charcoal is safe. Although there

are relatively few reports of adverse effects from the use of activated charcoal, there are numerous reports of complications,

usually involving aspiration. It is essential that the patient has an

intact or protected airway (intubation) before activated charcoal

is administered, especially in drowsy patients or patients who

may rapidly become obtunded.46

To see activated charcoal in a lung x-ray, go to

http://thepoint.lww.com/AT10e.

Vomiting with aspiration of activated charcoal occurs in about

5% of patients who receive activated charcoal.46,53–55 The resulting pulmonary problems can be caused by aspiration of acidic

stomach contents or the charcoal. Decreased oxygenation can

occur immediately, or pulmonary effects can occur later.55–59

Adult respiratory distress syndrome has resulted after the unintentional instillation of charcoal into the lung.55 Aspiration of

charcoal can result in chronic lung disease or fatalities, whereas

the toxic exposure, for which the charcoal was administered, is

often not lethal or even serious.56,60

Cathartics

Historically, sorbitol (a cathartic) was often administered with

activated charcoal to enhance passage of the charcoal-substance

complex through the GI tract. However, decreased transit time

through the bowel has not been proven to decrease absorption

as drug absorption does not take place in the large bowel.47 Sorbitol is also associated with vomiting and aspiration.47 Hypernatremia can also develop subsequent to the administration of

repeat doses of activated charcoal with sorbitol.61,62 Currently,

most EDs use aqueous activated charcoal mixtures rather than

charcoal–sorbitol combinations. Because cathartics are not effective in reducing drug absorption or increasing patient outcome,

their use is no longer advised.47

Whole Bowel Irrigation

Whole bowel irrigation with a polyethylene glycol–balanced

electrolyte solution (e.g., Colyte, GoLYTELY) can successfully

remove substances from the entire GI tract in a period of

several hours. WBI is effective with ingestions of sustainedrelease dosage forms, as well as substances that form bezoars

(concretions of tablets or capsules), such as ferrous sulfate or

phenytoin.26,48,63 WBI is also indicated when the toxic agent is

not adsorbed by activated charcoal (e.g., body-packer packets,

lithium, iron, potassium).25,26,48,63 This method of GI decontamination takes much longer to complete and is associated

with poor patient compliance because large volumes of fluid

(2 L/hour for adults until the effluent is clear) need to be ingested

to be effective.63 A nasogastric (NG) tube can be inserted, and

the WBI fluid can be administered via NG tube so that lack of

patient compliance is no longer a factor.48

ANTIDOTES AND SPECIFIC TREATMENTS

An antidote is a drug that neutralizes or reverses the toxicity

of another substance. Some antidotes can displace a drug from

receptor sites (e.g., naloxone for opioids, flumazenil for benzodiazepines), and some can inhibit the formation of toxic metabolites (e.g., N-acetylcysteine [NAC] for acetaminophen, fomepizole for methanol).26,64,65 Some treatments are highly effective

for the management of individual drug overdoses but do not

meet the definition of an antidote. For example, sodium bicarbonate is used to treat the cardiotoxicity arising from tricyclic

antidepressant (TCA) overdoses, and benzodiazepines are used

to treat CNS toxicity associated with cocaine and amphetamine

overdoses.26,66–68 However, it is important to note that for antidotes to be effective, they must be readily available at the health

care facility in adequate doses to treat the patient in a timely

manner.69

ENHANCING SYSTEMIC CLEARANCE

Hemodialysis and manipulation of urine pH can enhance

the clearance of substances. Hemodialysis can successfully

treat some specific intoxications (e.g., methanol, ethylene glycol, aspirin, theophylline, lithium). Hemodialysis can also be

used in patients with severe acid–base disturbances or renal

dysfunction.50 Alkalinization of the urine can enhance the elimination of drugs such as aspirin and phenobarbital.70–72

MONITORING OUTCOME

Selecting the appropriate parameters and length of time to

monitor a patient who has been exposed to a toxic agent

requires knowledge of toxic effects and the time course of the

intoxication.36,37 Most patients who are at risk for moderate or

severe toxicity should be monitored in an intensive care unit

(ICU) with careful assessments of cardiac, pulmonary, and CNS

function.73,74

ASSESSMENT OF SALICYLATE

INGESTION

Gathering a History

CASE 4-1

QUESTION 1: M.O., the mother of a 3-year-old child, states

that her daughter, D.O., has ingested some aspirin tablets.

What additional information should be obtained from or

given to M.O. at this time?

Obtaining an initial assessment of the patient’s status is essential. The caller’s telephone number should be obtained in the

event that the call is disconnected, initial recommendations need

to be modified, or subsequent follow-up is needed. The health

care provider should ask for patient-specific information with

questions that are nonthreatening and nonjudgmental. The caller

should be reassured that calling for help was the right thing

to do.

71Managing Drug Overdoses and Poisonings Chapter 4

Evaluating Clinical Presentation

CASE 4-1, QUESTION 2: On further questioning, M.O.

states that D.O. is crying and complaining of a stomachache.

Otherwise, the child appears to be acting normally. D.O.

was found sitting on the bathroom floor with an aspirin

bottle in her hand and some partially chewed tablets on

the floor next to her. M.O. states that the child had the

same look on her face that she has when she eats things

that she does not like. M.O. reports that she can see white

tablet material gummed on the child’s teeth. The mother

was gone no more than 5 minutes and had asked her 5- and

6-year-old sons to watch their sister. What additional information is needed to correctly assess the potential for

toxicity in D.O.?

To determine the potential toxicity for an unintentional ingestion, it is important to assess the presence of symptoms and to

identify the substance ingested. Inquiries should begin with openended questions to determine the facts that the caller is certain of

versus what may have been assumed. The answers usually point

to more specific information that is needed to accurately assess

the exposure.23

D.O.’s symptoms presently are not life-threatening. Her

behavior is consistent with being scared in response to the

mother’s anxiety. Once it has been established that the child does

not need immediate life-saving treatment, the caller is generally

more willing and able to answer additional questions.

M.O. already has provided information about the child’s

symptoms. More information is needed to determine the identity of the ingested substance, the time of ingestion, the brand of

aspirin (to ensure that the product is not an aspirin-combination

or even an aspirin-free formulation), the dosage form, the number of dosage units in a full container, and the number of remaining dosage units in the container. The parent should be careful to

look for tablets under beds, rugs, or other locations out of sight

(e.g., wastepaper baskets, toilets, pet food dishes, pockets). The

dosage forms in the container should be identical in appearance,

and the contents should be what are stated on the label. Information concerning the child’s weight and health status, as well

as whether the child is taking other medications, is also important. The child’s weight is useful in determining the maximum

milligram per kilogram dose of aspirin that was ingested.

When more than one child is present during an ingestion,

the caller should be questioned as to whether other children also